General and specific characteristics of modernization correlate with higher risk. A positive correlation between a country’s GDP per capita, as quantitative measure of modernization, and lifetime risk of a mood disorder trended toward significance (p=0.06). Mental and physical well-being are intimately related. The growing burden of chronic diseases, which arise from an evolutionary mismatch between past human environments and modern-day living, may be central to rising rates of depression. Declining social capital and greater inequality and loneliness are candidate mediators of a depressiogenic social milieu. Modern populations are increasingly overfed, malnourished, sedentary, sunlight-deficient, sleep-deprived, and socially-isolated. These changes in lifestyle each contribute to poor physical health and affect the incidence and treatment of depression. The review ends with a call for future research and policy interventions to address this public health crisis.